[Federal Register: August 30, 2001 (Volume 66, Number 169)]
[Notices]
[Page 45841-45843]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30au01-39]
[[Page 45841]]
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CONSUMER PRODUCT SAFETY COMMISSION
Poison Prevention Packaging; Notice of Stay of Enforcement for
Lidoderm Patch
AGENCY: Consumer Product Safety Commission.
ACTION: Stay of enforcement.
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SUMMARY: This notice announces the Commission's decision to stay
enforcement of special packaging requirements for the orphan drug,
Lidoderm. The Commission will stay enforcement under the
conditions stated at the end of this notice.
DATES: The stay will be effective on August 30, 2001.
FOR FURTHER INFORMATION CONTACT: Geri Smith, Office of Compliance,
Consumer Product Safety Commission, Washington, DC 20207; telephone
(301) 504-0608, extension 1160.
SUPPLEMENTARY INFORMATION:
A. Background
Under the Poison Prevention Packaging Act (``PPPA''), the
Commission has the authority to require special packaging for drugs (as
well as certain other household products) if it finds that child
resistant (``CR'') packaging is necessary to protect children from
serious personal injury or illness from handling using or ingesting the
drug and that CR packaging is technically feasible, practicable and
appropriate. 15 U.S.C. 1472(a). In 1995, the Commission issued a rule
requiring CR packaging for lidocaine products with more than 5
milligrams (mg) of lidocaine in a single package. 16 CFR 1700.14
(a)(23).
Lidoderm is a dermal patch that contains lidocaine. Each
Lidoderm patch contains 700 mg lidocaine. Lidoderm
is marketed in the form of five patches inside a non-CR resealable foil
envelope to maintain the integrity of the product. One non-CR carton of
Lidoderm contains six envelopes (each envelope contains five
patches) for a total of 30 patches per carton.
In May 1999, Commission staff discovered that Lidoderm
was being packaged in non-CR packaging and notified the distributor,
Endo Pharmaceuticals Inc. (``Endo'') of the special packaging
requirement for lidocaine products. To comply with the PPPA, the
immediate container for a product that requires special packaging must
be CR. Thus, for Lidoderm patches, each patch must be
packaged in an individual CR pouch or a single resealable CR pouch must
contain all of the patches (i.e., no carton and no foil envelope, only
a resealable CR pouch). At Endo's request, the Commission granted Endo
a temporary stay of enforcement on May 15, 2000, on the condition that
Endo provide pharmacists with an outer CR package to dispense the
product while it was developing a plan and timeline to package each
patch in a CR pouch.
On August 14, 2000, Endo petitioned the Commission for a partial
exemption for Lidoderm from special packaging requirements
stating that ``it is not practicable to market each Lidoderm
patch in a child-resistant envelope.'' The petitioner argues that to do
so is cost prohibitive and would force it to discontinue production of
Lidoderm. Endo asks for an exemption so that it may replace
the non-CR carton with the CR pouch so that the six envelopes (5
patches per envelope) are marketed in the CR pouch, not in the non-CR
carton.
B. The Product
Lidoderm is a lidocaine-containing dermal patch available
only by prescription. It is manufactured by Teikoku Seiyaku, Co., Ltd.,
a Japanese company, and the only manufacturer the Food and Drug
Administration (``FDA'') has approved to manufacture
Lidoderm. Endo is the only distributor the FDA has approved
for Lidoderm. The FDA designated Lidoderm as an
orphan drug on October 24, 1995 and approved it for marketing on March
19, 1999. Endo started marketing Lidoderm on September 15,
1999. Orphan drugs are intended for rare diseases affecting less than
200,000 people or affecting more than 200,000, but for which there is
no expectation that the costs of drug development will be recovered
from sales. The Orphan Drug Act encourages the development of orphan
drugs, through economic incentives such as tax credits for clinical
research and seven years of marketing exclusivity.
Lidoderm is prescribed to treat post-herpetic neuralgia
(``PHN''), a rare, chronic condition that results from nerve injury
caused by shingles. Shingles occurs following reactivation of the
herpes zoster virus (the same virus responsible for chickenpox) and is
characterized by painful fluid-filled skin blisters. PHN is more common
in the elderly. Approximately 10% of all patients with shingles develop
PHN. Endo estimates that about 200,000 Americans have PHN. There is no
cure for PHN, and treatment is aimed at controlling the pain by various
methods including drug therapy (e.g., analgesics, antidepressants,
topical anesthetics, and anticonvulsants), acupuncture, and nerve
block.
Each carton of Lidoderm contains 30 patches packaged in
six resealable foil envelopes with five patches per envelope. Neither
the carton nor the individual envelopes are CR. Currently, Endo is
including a CR reclosable pouch large enough for the six envelopes in
each carton. Each Lidoderm patch is 22 square inches (10 cm x
14 cm) and contains 700 mg of lidocaine. The amount of lidocaine
systemically absorbed from Lidoderm depends on both the
duration of exposure and the surface area of skin covered. The
recommended dose is up to three patches at one time only once for up to
12 hours in a 24-hour period. Patches may be cut into smaller sizes
prior to removal of the release liner. The petitioner did not provide
data related to the stability of the lidocaine in a cut or used patch,
but instructions on the product envelope advise that the patch adhesive
contains water and will dry out if the package is left open.
According to the petition, Lidoderm is unlike other patch
systems in that the lidocaine in Lidoderm is not contained in
a reservoir, but is embedded in the patch adhesive. Therefore, the
patch releases a low level of lidocaine into the skin over a long time
period ensuring that it produces analgesia (pain reduction) rather than
anesthesia (numbness). Since only a small percentage (3%
2%) of lidocaine is absorbed dermally from the Lidoderm patch
when used therapeutically, about 95% of the lidocaine will remain in a
used patch. Endo states that the lidocaine is less accessible from this
patch system than from other formulations (such as, creams and liquids)
and that a child would need to chew or suck on the patch for some time
before any lidocaine would be absorbed through the mouth or swallowed.
However, there are no oral absorption data indicating the extent of
oral exposure necessary for a child to absorb a toxic dose. Endo
provides a warning with the product to store and dispose of
Lidoderm out of the reach of children and pets.
C. Endo's Request
In its petition, Endo asks essentially that the temporary stay of
enforcement granted by the Commission on May 15, 2000, be made a
permanent exemption from special packaging requirements. Endo argues
that full compliance with the PPPA, which requires that the immediate
container of a lidocaine-containing drug be CR, would be cost-
prohibitive. Endo maintains that the costs of new equipment, plant re-
engineering, and testing for FDA approval are prohibitive and would
[[Page 45842]]
force them to discontinue marketing Lidoderm. Teikoku
estimates a large total cost for the changes required to place each
patch in a CR pouch. This includes the cost of: (1) New envelope
processing machines; (2) producing three FDA submission batches; (3)
extended specification compliance testing on all three batches; (4)
accelerated stability testing; and (5) real-time stability testing. The
petitioner maintains that ``manufacturing and packaging one patch per
envelope would result in a significant increase in the cost of
manufacturing Lidoderm because there would be significant
increases in the amount of labor and materials.''
Endo also argues that it would take much longer than the current
packaging method to produce an equivalent amount of Lidoderm
in individual CR pouches. Endo states that this change in the
production schedule for Lidoderm is an ``undue burden'' for
Teikoku because it would affect Teikoku's production of other products.
Teikoku is unwilling to allow another manufacturer to take over
production because the manufacturing process for Lidoderm is
proprietary. CPSC has not been able to verify the accuracy of Endo's
cost estimates. However, Endo maintains that it will discontinue
production of Lidoderm if forced to place each patch in CR
packaging. If that were to happen, Lidoderm would no longer
be a therapeutic option for PHN patients.
D. PPPA Requirements for an Exemption
The Commission's regulations provide for a company or other
interested persons to submit a petition requesting an exemption from
PPPA requirements. 16 CFR part 1702. Those rules require a petitioner
to provide a justification for the exemption based on one or more of
the following grounds: (1) Special packaging is not necessary to
protect children from serious injury or illness from the substance; (2)
special packaging is not technologically feasible, practicable, or
appropriate for the substance; and/or (3) special packaging is
incompatible with the substance. 16 CFR 1702.7. Similarly, the
Commission's rules provide that if the Commission finds that a
petitioner has presented ``reasonable grounds'' for an exemption, it
shall publish a proposed amendment exempting that substance from
special packaging requirements.
``Reasonable grounds'' are:
Information and data sufficient to support the conclusion that:
(a) The degree or nature of the hazard to children in the
availability of the substance, by reason of its packaging, is such
that special packaging is not required to protect children from
serious personal injury or serious illness resulting from handling,
using, or ingesting the substance, or
(b) Special packaging is not technically feasible, practicable,
or appropriate for the substance, or
(c) Special packaging is incompatible with the particular
substance.
16 CFR 1702.17.
In its petition, Endo states as its justification that ``it is not
practicable to market each Lidoderm patch in a child-
resistant envelope.'' Endo argues that the high cost and practicable
difficulties, discussed above, of packaging each individual
Lidoderm patch in a CR container justify an exemption.
Endo states that there have been no reports of adverse events or
accidental exposures of Lidoderm to children. Although Endo
states that Lidoderm does not present the same degree of
poisoning risk to children as other lidocaine products, Endo does not
argue and does not provide any data indicating that the lidocaine in
Lidoderm patches is not toxic to children. Thus, Endo does
not seem to be relying on lack of toxicity to children as a
justification for an exemption.
Legislative history of the PPPA indicates that the term
``practicability'' means that ``special packaging meeting the standard
would be susceptible to modern mass-production and assembly-line
techniques.'' S. Rep. 845 91st Cong., 2d Sess 10 (1970). Endo does not
argue that Lidoderm cannot be produced with CR packaging that
complies with the PPPA. Rather, Endo asserts that such packaging would
be so costly that it could not continue to market Lidoderm.
Thus, the Commission cannot make the requisite finding that CR
packaging would not be practicable for Lidoderm that would
justify an exemption under the Commission's regulations.
E. Stay of Enforcement
Endo has, however, presented information indicating the need for
the orphan drug Lidoderm, the prohibitive cost involved in CR
packaging for each Lidoderm patch, the limited market for the
product, and the protection for children that would be provided by
packaging Lidoderm patches in an outer CR package. The
Commission finds that these circumstances justify the stay of
enforcement. The stay will be issued with the following conditions:
1. Endo Pharmaceuticals must, as stated in section IV of the
petition, ``replace the outer carton for Lidoderm with a CR
reclosable pouch containing six resealable foil envelopes (5 patches
per envelope)'' with instructions to pharmacists that they must
dispense Lidoderm envelopes in the outer pouch. Moreover,
additional outer CR pouches must be provided to pharmacists upon
request in order to accommodate prescriptions of less than a full
package of 30 patches.
2. The outer CR package must bear a prominent and conspicuous label
stating the following:
``WARNING:
New and used patches could harm small children if chewed or
swallowed. Envelopes in this package are NOT child resistant. You
MUST keep envelopes inside this child-resistant package with the
zipper closed.
Keep new and used patches out of the reach of children.''
3. The envelopes containing the five Lidoderm patches
(the immediate packaging) must continue to bear the warning label
``Package not child resistant. Keep used and unused patches out of the
reach of children.''
4. Lidoderm must remain designated by the FDA as an
orphan drug indicated solely for the treatment of PHN. If Endo obtains
orphan drug status for Lidoderm for the treatment of any
other condition, Endo shall direct to the Commission's Office of
Compliance, a request for a determination of whether the terms of this
stay shall apply to the product.
5. Lidoderm must be manufactured only by Teikoku Seiyaku
Co., Ltd, at its present location in Japan under the current material
operating conditions and procedures described in Section V of the
petition. Any questions related to changes in such operating conditions
or procedures can be directed to the Commission's Office of Compliance.
6. Endo Pharmaceuticals must (1) notify the Commission's
Directorate for Health Sciences within five business days of becoming
aware of any poisonings or other exposures (i.e., physical contact) to
the patches by children under 5 years old; and (2) purchase American
Association of Poison Control Center data for Lidoderm once a
year and submit it to the Commission's Directorate for Health Sciences.
7. Endo must report annually to the Office of Compliance confirming
that the conditions upon which the stay has been granted remain in
effect. Additionally, Endo must notify the Office of Compliance 30 days
in advance of any change that materially affects its compliance with
any provision of the stay.
[[Page 45843]]
Dated: August 24, 2001.
Todd Stevenson,
Acting Secretary, Consumer Product Safety Commission.
[FR Doc. 01-21880 Filed 8-29-01; 8:45 am]
BILLING CODE 6355-01-P